CN105597146B - Wound healing multi-functional temperature sensitive gel composite dressing and its preparation and application method - Google Patents
Wound healing multi-functional temperature sensitive gel composite dressing and its preparation and application method Download PDFInfo
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- CN105597146B CN105597146B CN201610038682.4A CN201610038682A CN105597146B CN 105597146 B CN105597146 B CN 105597146B CN 201610038682 A CN201610038682 A CN 201610038682A CN 105597146 B CN105597146 B CN 105597146B
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- temperature sensitive
- wound healing
- dressing
- gel composite
- wound
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- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A—HUMAN NECESSITIES
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
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Abstract
The invention discloses a kind of wound healing multi-functional temperature sensitive gel composite dressing and its preparations and application method.The dressing includes n-trimethyl chitosan chloride derivative and terminal aldehyde group temperature sensitive polymer, and the mass ratio of two kinds of components is 1:15~1:25；Wherein, the molecular weight of the chitosan of n-trimethyl chitosan chloride is used to prepare between 10~1,000,000, and deacetylation is 90% or more, and quaternized degree of substitution is 10%~45%.The dressing is the viscous liquid of wound easy to apply at room temperature, and gel membrane coat can be quickly formed in 1 minute after smearing wound.Not only had from antibacterial anti-inflammatory performance and good film forming stability based on thermo-sensitive gel compound dressing prepared by the present invention, wet environment and drug controlled-releasing function can also be provided, can be used for the therapeutic wound healings such as diabetic foot ulcer.
Description
Technical field
The invention belongs to biomedical materials fields, and in particular to a kind of multi-functional temperature sensitive gel composite of wound healing
Dressing and its preparation and application method.
Background technology
Skin is first of barrier of human defense's function and first of immune defence line of human body, is ceased with health
Manner of breathing closes.But be difficult to avoid that various incised injuries, scratch, burn and chemical burn etc. in living, wound once being formed easily by
The invasion such as pathogenic microorganism；Especially for diabetic, tiny wound easily leads to further ulcer, and then is formed
Diabetes, severe patient may lead to amputation.
On the one hand ideal wound dressing wants that ulcer secondary infection can be controlled, on the other hand want wound can be promoted quickly to be cured
It closes.The medical dressing that developed recently gets up includes mainly film (the protection surface of a wound), foam (protection, absorbs filling), hydrogel
(debridement, rehydration, moisturizing), hydrocolloid (debridement, protection) etc..Wherein, hydrogel is formed by processing of high molecular material, can be inhaled
Wound exudate is received, and liquid permeable portion can be retained in dressings, so that the surface of a wound is generated micro- wet, slightly sour and low-oxygen environment, promotes tissue
Reparation and re-epithelialization；Moreover, using the porous network structure of hydrogel, it can also embed that some can accelerate wound with controlled release
The drug of healing, thus paid close attention to by people, but at present following main problem is still had in the area research and clinical application：One
It is that existing aerogel dressing itself does not have antibacterial functions, the nano silver etc. for generally requiring additional a large amount of antibiotic or easily reuniting
Antimicrobial component, as disclosed in patent CN105079862A " a kind of medical antibacterial dressing and preparation method thereof ", patent
" a kind of silver-containing antibacterial dressing and preparation method " disclosed in CN104857551A etc. is using nano silver as antibacterial additives；Second is that right
Wound scribble effect is not ideal enough, and molded aerogel dressing is difficult to even application in wound surface at room temperature, and mechanical property
The poor aerogel dressing of energy is then difficult to form stable coating in wound surface, its application is caused to be restricted.
Invention content
To solve the disadvantage that the prior art and shortcoming, the primary purpose of the present invention is that providing a kind of wound healing use
Multi-functional temperature sensitive gel composite dressing.The dressing is by a kind of n-trimethyl chitosan chloride derivative and a kind of temperature sensitive polymerization of terminal aldehyde groupization
Object is uniformly mixed formation after being dissolved in water, is the viscous liquid of wound easy to apply under room temperature (25 DEG C), can be at 1 point after smearing wound
Stable gel membrane coat is quickly formed in clock, while being had both from antibacterial anti-inflammatory performance and drug controlled-releasing function, especially suitable for
The therapeutic wound healings such as diabetic foot ulcer.
Wound healing provided by the invention is different from existing aerogel dressing with multi-functional temperature sensitive gel composite dressing,
Can be by the heat-induced gel characteristic of schiff base reaction self-crosslinking and temperature sensitive component between two components, smearing, wound surface is fast
Speed forms gel coat, has both avoided the use of potentially toxic chemical cross-linking agent, while dressing coat also being made to have excellent power
Learn stability；Meanwhile system itself has excellent anti-microbial property, is not required to the antiseptics such as outer added with antibiotic, nano silver, it can be effective
Ground avoids wound from further infecting；In addition, be the viscous liquid for tending to smear out wound before dressing contact wound, once it smears
Stable gel coat can be quickly formed after wound, be not only convenient for smearing wound when clinical application, but also convenient for addition and controlled release medicine
Object (embodiment 1), growth factor (embodiment 4) isoreactivity substance are more advantageous to promotion wound healing.
Chitosan as wound healing one of multi-functional temperature sensitive gel composite dressing raw material derives from nature, peace
Atoxic has extraordinary biocompatibility and degradability, and derives from a wealth of sources, cheap.After chemical reaction can synthesize
N-trimethyl chitosan chloride derivative (HTCC) with antibacterial functions, the Pluronic F127 (F127-CHO) of they and aldehyde radical
Self-crosslinking in situ is acted on by schiff bases, is conducive to the performance for improving Pluronic temperature sensitive type in-situ hydrogels, such as improves gel
Change temperature, the performance etc. of hydrogel stability and slow releasing pharmaceutical.
Another object of the present invention is to provide a kind of wound healing preparations of multi-functional temperature sensitive gel composite dressing
Method.
It is still another object of the present invention to provide the above-mentioned wound healing uses of multi-functional temperature sensitive gel composite dressing
Method.
The object of the invention is achieved through the following technical solutions：
A kind of multi-functional temperature sensitive gel composite dressing of wound healing, which includes n-trimethyl chitosan chloride derivative
(HTCC) and terminal aldehyde group temperature sensitive polymer (F127-CHO), the mass ratio of two kinds of components is 1:15~1:25；Wherein, for making
The molecular weight of the chitosan of standby n-trimethyl chitosan chloride is between 10~1,000,000, and deacetylation is 90% or more, quaternized substitution
Degree is 10%~45%.
The n-trimethyl chitosan chloride derivative (HTCC) itself has anti-microbial property, is not required to outer added with antibiotic, nano silver
Equal antiseptics are conducive to control wound infection.
The wound healing is at room temperature the viscous liquid of wound easy to apply with multi-functional temperature sensitive gel composite dressing,
Gel membrane coat can be quickly formed in 1 minute after smearing wound, can be used for the therapeutic wound healings such as diabetic foot ulcer.
A kind of wound healing preparation method of multi-functional temperature sensitive gel composite dressing, includes the following steps：
(1) 20~200 mass parts n-trimethyl chitosan chloride derivatives (HTCC) are weighed, 1~10 parts by volume buffer solution is added,
Heating stirring dissolves, and n-trimethyl chitosan chloride derivative solution is made；
(2) weigh 300~5000 mass parts terminal aldehyde group temperature sensitive polymers (F127-CHO) keeps its molten in low temperature
Solution in buffer solution, it is to be dissolved completely after, the n-trimethyl chitosan chloride derivative being added obtained by step (1) by a certain percentage is molten
Liquid, low temperature stir and evenly mix, ageing, and mixed system I is made, and the as described wound healing is applied with multi-functional temperature sensitive gel composite
Material.
N-trimethyl chitosan chloride derivative of the present invention is to contain hydroxypropyl-trimethyl ammonium chloride on a kind of chitosan sugar chain
The water-soluble polymer of functional group is obtained by 2,3- epoxypropyltrimethylchloride chloride modification of chitosan, it is preferable that for making
The viscosity-average molecular weight of the chitosan of standby step (1) the n-trimethyl chitosan chloride derivative is 10~1,000,000, and deacetylation is
90% or more, quaternized degree of substitution is 10%~45%.
To make n-trimethyl chitosan chloride derivative fully dissolve, its polymer segment is made fully to unfold and aldehyde radical Pluronic
Schiff bases occur to act on forming relatively stable in-situ hydrogel, as a preferred embodiment, step (1) and step (2) are described
Buffer solution is disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution (pH=7.4), acetic acid-sodium acetate buffer solution (pH=6.8), lemon
Lemon acid-sodium citrate buffer solution (pH=7.2) or citric acid-sodium hydroxide-hydrochloride buffer (pH=7.0), buffer solution can
It is dissolved in the case where not destroying the heating condition of n-trimethyl chitosan chloride derivant structure and performance；Step (1) described heating stirring
The temperature of dissolving is 25~60 DEG C, and the time is 12~36 hours.
Terminal aldehyde group temperature sensitive polymer (F127-CHO) described in step (2) is prepared by following steps：
The acetic anhydride of 10 times of moles is added in Pluronic F127, DMSO (dimethyl sulfoxide (DMSO)) is slowly dropped under stirring and is dissolved, 20~
6~12h is reacted at 50 DEG C；After low-temperature centrifugation, supernatant precipitates with anhydrous ether, and suction filtration is dried to obtain F127-CHO.
Schiff base reaction can occur with HTCC for gained F127-CHO, and micro- be cross-linked to form in part tends to smear out wound at room temperature
Viscous liquid, in combination with Pluronic F127 heat-induced gels characteristics after smearing wound quickly formed have well at
The gel coat of membrane stability had both avoided the use of potentially toxic chemical cross-linking agent, while it is excellent also to have dressing coat
Mechanical stability.
Preferably, the low temperature described in step (2) is set as 4~15 DEG C, the reason is that, (1) Pluronic F127 are amphiphilic
Property polymer, stirring at normal temperature easily generate a large amount of bubbles, influence the preparation effect of hydrogel；(2) temperature is lower, Pluronic
F127 solution viscosities are smaller, are easy to interact with n-trimethyl chitosan chloride derivative, improve the stability of hydrogel.
In order to make schiff bases key, the reaction was complete, and low temperature stirs and evenly mixs the mixed solution of gained at low temperature in step (2)
Ageing 12~for 24 hours, and study whether in-situ hydrogel can occur gelation near body temperature, the study found that the system is solidifying
Gelatinization temperature is preferably 28~35 DEG C, close to human surface temperature.
In above-mentioned preparation method, the rotating speed of the stirring is both preferably 100~1000 revs/min.
Above-mentioned wound healing can be used alone with multi-functional temperature sensitive gel composite dressing, can also add other external used medicines
After use.
Exclusive use refers to that mixed system I is directly applied to skin or other heat sources, can be formed with temperature change
HTCC/F127-CHO gel composites.
The step of adding use after other external used medicines is as follows：
(1) 1-100 milligrams of drugs (such as Ofloxacin) are weighed, the wound healing of solution state is added with multi-functional temperature sensitive solidifying
Glue compound dressing, low temperature stirring thoroughly dissolving, is made mixed system II, is wound easy to apply under room temperature condition (25 DEG C)
Viscous liquid；
(2) the mixed system II obtained by step (1) is applied to skin or other heat sources, can be formed with temperature change
HTCC/F127-CHO gel composites.
Compared with prior art, the present invention has the following advantages and beneficial effects：
(1) present invention prepares temperature sensitive type in-situ hydrogel jointly by n-trimethyl chitosan chloride derivative and F127-CHO,
Gelling temperature is 28~35 DEG C, close to human surface temperature, can form hydrogel in 1 minute at 37 DEG C.With it is simple
Pluronic F127 system in-situ hydrogels are compared, HTCC/F127-CHO system in-situ hydrogels have higher stability,
Shorter gelation time and longer medicament slow release time, to realize that medicament slow release provides possibility.
(2) wound healing that the present invention prepares has antibiotic property with multi-functional temperature sensitive gel composite dressing system itself
Can, the antiseptics such as outer added with antibiotic, nano silver are not required to, are conducive to control wound infection.
(3) present invention's is simple for process, and easy to operate, required equipment and raw material are cheap.
(4) wound healing prepared of the present invention cannot be only used for wound with multi-functional temperature sensitive gel composite dressing and be cured
It closes, is expected to be used for percutaneous dosing and injection delivery systems, thus there is certain application prospect in terms of new medicinal preparation.
Description of the drawings
Fig. 1 is the schematic diagram for preparing the multi-functional temperature sensitive gel composite dressing of wound healing.
Fig. 2 is hydrogel drug release patterns in vitro：■ F127-CHO/ Ofloxacin composite hydrogels；▲HTCC/
F127-CHO/ Ofloxacin composite hydrogels.
Fig. 3 is the Bactericidal test of hydrogel：A) hydrogel composites photomacrograph, b) F127-CHO hydrogels are antibacterial
Circle, c) HTCC/Pluronic F127 hydrogel inhibition zones, d) HTCC/F127-CHO hydrogel inhibition zones.
Fig. 4 is HTCC/F127-CHO hydrogel stereoscan photographs.
Fig. 5 is HTCC/F127-CHO Hydrogel In Treating diabetes mouse wound model photos (upper left：Independent hydrogel
Before treatment, lower-left：Independent Hydrogel In Treating is after 7 days, upper right：Before hydrogel and growth factor combination therapy, bottom right：Hydrogel with
After growth factor combination therapy 7 days).
Specific implementation mode
With reference to embodiment and attached drawing, the present invention is described in further detail, but embodiments of the present invention are unlimited
In this.Unless stated otherwise, reagent involved in embodiment, method are reagent and method commonly used in the art.
Embodiment 1
(1) chitosan that viscosity-average molecular weight is 100,000 is dissolved in 1~3% acetic acid solution, stirring and dissolving instills lye tune
PH=8~10 are saved, there is white precipitate precipitation, impregnate 6~12h, are filtered, deionized water is washed till neutrality, drains, to white depositions
Middle addition 30~100mL isopropanols stir evenly, and are warming up to 50~90 degrees Celsius, every 1~2h, instill 2, the 3- rings of 1g/mL
Oxygen propyl group trimethyl ammonium chloride (Glycidyltrimethylammonium chloride, GTA) solution, point 2~4 progress,
3~8mL every time, and every time the time be not less than 0.5h, the reaction was continued after the completion of addition 8~for 24 hours, after reaction, be added 200~
500mL acetone precipitations obtain the product in a vacuum and drying environment 2- hydroxypropyltrimethylammonium chloride chitosan (HTCC).
(2) acetic anhydride of 10 times of moles is added in Pluronic F127, is dissolved with 50~200mL DMSO, magnetic force
It is slowly dropped under stirring, reacts 12h at 20 DEG C.After low-temperature centrifugation, supernatant precipitates with anhydrous ether, and suction filtration obtains white
Precipitation, is dried to obtain aldehyde radical Pluronic (F127-CHO).
(3) 200 milligrams of n-trimethyl chitosan chloride derivatives (2- hydroxypropyl-trimethyl ammonium chloride shells made from step (1) are weighed
Glycan), it is placed in serum bottle, 1 milliliter of disodium hydrogen phosphate-sodium dihydrogen phosphate buffer (pH=7.4), heating stirring is added
(100~1000 revs/min of rotating speed) dissolves 12-36 hours, and n-trimethyl chitosan chloride derivative solution is made；
(4) F127-CHO made from 3.0 grams of steps (2) is weighed in disodium hydrogen phosphate-sodium dihydrogen phosphate buffer (pH=
7.4) in after dissolving completely, the n-trimethyl chitosan chloride derivative solution obtained by addition step (3), low temperature stirring (rotating speed 100~
1000 revs/min) dissolving, it is aged 24 hours, mixed system I is made, system total volume is 12mL；
(5) 120 milligrams of Ofloxacins are weighed, above-mentioned mixed system I is added, low temperature stirs (100~1000 revs/min of rotating speed)
Mixed system II is made in dissolving 12 hours.
(6) gained mixed system II is placed in water bath device, increases temperature, stirred (100~1000 revs/min of rotating speed), led to
It crosses inversion bottleneck method and measures gelling temperature and gelation time, HTCC/F127-CHO temperature sensitive type in-situ hydrogels are made；
(7) in-situ hydrogel for preparing step (6) is packed into bag filter (6000~15000 dalton of molecular weight of shutting off),
It is measured at 37 DEG C in disodium hydrogen phosphate-sodium dihydrogen phosphate buffer (pH=7.4) (volume ratio 1:9) the drug body in
Outer release behavior calculates drug and adds up release rate, draws drug release in vitro curve, as shown in Figure 2.
Fig. 2 is the in-situ hydrogel accumulative release rate of Ofloxacin and the relational graph of time, root in simulating release solution
The accumulative release rate of Ofloxacin can be calculated according to formula (1).The result shows that the time of hydrogel sustained release Ofloxacin is about 30
Hour, than (8 hours) length of slow-release time of Pluronic F127/ Ofloxacin in-situ hydrogels.This may be also due to
There are the reasons of schiff bases effect between F127-CHO and HTCC.
Accumulative release rate %=(Wt/ W) × 100% (1)
In formula, WtFor the drug weight that t moment solution releases, W is the total weight of the drug of load.
Embodiment 2
(1) it weighs the chitosan (deacetylation is more than 95%) that 3g viscosity-average molecular weights are 120,000 and is dissolved in the acetic acid of 100mL2%
Dissolving is stirred at room temperature in aqueous solution, and 10mL GTA aqueous solutions (1g/mL) are slowly added dropwise with dropping funel, the reaction was continued 1h, cold
But it is slowly dropped into ice acetone and precipitates afterwards, 10h is stood at 4 deg. celsius after the completion of precipitation, be filtered to remove acetone, heat is used after dry
Ethyl alcohol reacts for 24 hours in Soxhlet extractor, and vacuum drying obtains n-trimethyl chitosan chloride derivative；
(2) n-trimethyl chitosan chloride derivative made from 60 milligrams of steps (1) is weighed, is placed in serum bottle, 1 milliliter of second is added
Acid-sodium acetate buffer (pH=6.8), 30 DEG C of heating stirring (100~1000 revs/min of rotating speed) dissolvings, it is poly- to be made quaternized shell
Sugar derivatives solution；
(3) 1.2 grams of F127-CHO are weighed, are placed in beaker after being completely dissolved with acetic acid-sodium acetate buffer solution, wherein
Preparing for F127-CHO is as follows：The acetic anhydride that 10 times of moles are added in 5g Pluronic F127 is weighed, it is molten with 50mL DMSO
It solves, reacts 12h at 25 DEG C.After low-temperature centrifugation, supernatant 500mL anhydrous ethers precipitate, are dried to obtain after suction filtration.It is added
N-trimethyl chitosan chloride derivative solution obtained by step (2), low temperature stir (100~1000 revs/min of rotating speed) dissolving, are aged 12 overnight
Hour, mixed system I is made, system final mass is 6 grams；
(4) solution (mixed system I) prepared is put into water-bath gradually heating to heat, at regular intervals, is taken out
Test tube inclination sees if there is liquid flowing, does not keep the temperature 30min or more if flowing if observation gel, pats test tube later
Phenomenon is observed, preliminary judgement has become gel if gel internal liquid also no longer flows.
(5) it is measured using the advanced rotational rheometer of TA companies of U.S. ARES/RFS types, the tablet that fixture is 25mm presss from both sides
Have, mixed system I is uniformly dropped on tablet at 15 DEG C, is measured under dynamic time scan pattern at once, measuring condition
For frequency (Frequency)：1rad/s, deformation (Strain)：0.5%, the spacing (Gap) of plate jig is 1mm, into trip temperature
Scanning scans temperature range：18~40 DEG C, heating rate is 0.5 DEG C/min, fixed strain 0.5%, fixed dynamic frequency (ω)
For 1.0rad/s.For when the mass fraction 20% of Pluronic F127 or F127-CHO, phase transition temperature record such as table 1
It is shown：
1 phase transition temperature of table
(6) by after above-mentioned hydrogel liquid nitrogen quick freeze, vacuum freeze drying is sliced scanning electron microscope (SEM) after metal spraying
Lower observation, the size by the hole of hydrogel it can be seen from SEM photograph Fig. 4 is about between 10~200 μm.In addition, identical
Under F127-CHO concentration, with the increase of HTCC, the hole diameter of gel is reduced, show the crosslink density of hydrogel with
The increase of HTCC and increase.Show the concentration by HTCC, the cross-linked network structure that can be formed to hydrogel is adjusted.
Embodiment 3
(1) acetic acid aqueous solution that chitosan of the 5g deacetylations more than 95% is dissolved in 150mL 2% is weighed, at 80 degrees Celsius
17mL GTA aqueous solutions (1g/mL) are slowly added dropwise with dropping funel in lower stirring and dissolving, the reaction was continued 2h, are slowly dropped into after cooling
It is precipitated in ice acetone, 5h is stood at 4 deg. celsius after the completion of precipitation, be filtered to remove acetone, carried in Soxhlet with hot ethanol after dry
It takes and reacts 48h in device, vacuum drying obtains n-trimethyl chitosan chloride derivative；
(2) n-trimethyl chitosan chloride derivative made from 50 milligrams of steps (1) is weighed, is placed in serum bottle, citric acid-is added
(100~1000 revs/min of rotating speed) dissolving is stirred at room temperature in sodium hydroxide-hydrochloride buffer (pH=7.0), and n-trimethyl chitosan chloride is made
Derivative solution；
(3) 0.9 gram is weighed through the acetic anhydride-modified commercial product Pluronic F127 i.e. temperature sensitive polymerization of gained aldehyde radical
Object F127-CHO is placed in tool plug test tube, addition step complete with citric acid-sodium hydroxide-hydrochloride buffer (pH=7.0) dissolving
Suddenly n-trimethyl chitosan chloride derivative solution obtained by (2), low temperature stir (300 revs/min of rotating speed), are aged 15 hours after evenly mixing,
Mixed system I is made, two constituent content ratios are 1:18.
(4) bacteriostatic activity of chitosan is related with its cationic and bacterium self structure, in chitosan molecule chain-
NH2Formation-NH can be protonated in acid condition3+Cation, and bacterium surface is in electronegativity more, can be generated with bacterium surface
Electrostatic interaction forms a floor height molecular complex, its eucaryotic cell structure is destroyed, to play the role of restraining and sterilizing bacteria, through quaternized
Stronger quaternary ammonium salt group-the CH of electropositive is introduced after reaction2CH(OH)CH2N(CH3)3+, make it easier to be adsorbed in strain table
Face makes somatic cells film function get muddled, to inhibit its activity.We lead to using staphylococcus aureus as research object
Cross the antibacterial functions that Bactericidal test characterizes hydrogel.Sterilized ordinary nutrient agar conduct is added in sterile petri dish
Culture medium is allowed to entirely cover entire culture dish bottom, then thickness about 2-2.5mm is uniformly coated with a certain amount of on its surface
Staphylococcus aureus liquid forms bacterium solution film.The circular hole for making a call to a diameter 7.0mm with card punch at culture dish center, by mixture
It is I filling circular holes, smoothes out.Then sample is cultivated for 24 hours under the conditions of 37 DEG C, observes the growth shape of gel sample surrounding bacterial
Condition measures inhibition zone size.
From result figure 3 as can be seen that the Pluronic F127 gels without HTCC do not inhibit staphylococcus aureus
Effect, and then occur apparent inhibition zone around the Pluronic F127 gel hydrogels containing HTCC, illustrate this temperature sensitive water-setting
Glue has apparent antibacterial action.Discovery is measured by the size to inhibition zone, uses the Pluronic F127 of terminal aldehyde group
(F127-CHO) it has a certain impact to the bacteriostasis property of hydrogel, this may be to cause because aldehyde radical is reacted with part amino
Antibacterial functions slightly decline, but entirety still has good anti-microbial property.
Embodiment 4
(1) acetic acid aqueous solution that chitosan of the 5g deacetylations more than 95% is dissolved in 150mL 2% is weighed, at 80 degrees Celsius
17mL GTA aqueous solutions (1g/mL) are slowly added dropwise with dropping funel in lower stirring and dissolving, the reaction was continued 2h, are slowly dropped into after cooling
It is precipitated in ice acetone, 5h is stood at 4 deg. celsius after the completion of precipitation, be filtered to remove acetone, carried in Soxhlet with hot ethanol after dry
It takes and reacts 48h in device, vacuum drying obtains n-trimethyl chitosan chloride derivative；
(2) n-trimethyl chitosan chloride derivative made from 200 milligrams of steps (1) is weighed, is placed in serum bottle, is added 1 milliliter
N-trimethyl chitosan chloride derivative solution is made in disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution (pH=7.4) stirring and dissolving；
(3) 4.50 grams of F127-CHO are weighed, disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution (pH=7.4) is added and has dissolved
N-trimethyl chitosan chloride derivative solution obtained by step (2) is added in Quan Hou, and low temperature stirs (1000 revs/min of rotating speed) uniformly, and low temperature is old
Change 12 hours, mixed system I, volume 25mL is made, a certain amount of epidermal growth factor is added, is uniformly mixed obtained mixed system
II is preserved under low temperature；
(4) 250~300 grams of cleaning grade SD rats, after adaptability is raised 1 week, continuous 3d intraperitoneal injections 35mg/kg STZ
Induced diabetes, inject 3d after tail vein blood detect random blood glucose level, random blood glucose level >=16.7mmol/L after injection,
It is considered as diabetes model to be successfully established.Ad lib, drinking-water, body weight monitored weekly and blood glucose, root during diabetes rat is tested
Insulin isophane (NPH) 1-2U/d is subcutaneously injected according to blood glucose level, blood glucose maintains 16.7mmol/L~28mmol/L.Sugar
After the sick rat of urine was at mould 6 weeks, amobarbital 30mg/kg intraperitoneal injection of anesthesia, back cropping, 75% alcohol disinfecting is with the length of side
The disinfection template of 2.0cm as mark scalpel mouse back hit exactly formed at 1cm after skull a 2.0cm ×
The square wound of 2.0cm, excision extension is as deep as fascia, wound each mouse single cage raising after being formed.Wound is as shown in Figure 5.
(5) wound is smeared every other day with PBS solution and mixed system I and mixed system II respectively, after Wound healing and bone regeneration 7d
Wound shooting (A610, Canon) is carried out with digital camera, while placing one to have Scale ruler.Wound area Image J
(1.36b versions) is calculated.Multifunctional medical temperature-sensitive hydrogel compound is used alone as shown in Figure 5 to also show that significantly
Promote wound healing effect, wound healing rate reaches 80.6% after seven days.At the same time, in hydrogel composites addition epidermis life
Long agents treatment, wound healing rate can reach 88.7% after treatment seven days.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other it is any without departing from the spirit and principles of the present invention made by changes, modifications, substitutions, combinations, simplifications,
Equivalent substitute mode is should be, is included within the scope of the present invention.
Claims (7)
1. a kind of wound healing preparation method of multi-functional temperature sensitive gel composite dressing, which is characterized in that including following step
Suddenly：
(1) 20~200 mass parts n-trimethyl chitosan chloride derivatives are weighed, 1~10 parts by volume buffer solution is added, heating stirring is molten
N-trimethyl chitosan chloride derivative solution is made in solution；
(2) 300~5000 mass parts terminal aldehyde group temperature sensitive polymer low temperatures are weighed to make it dissolve in buffer solution, are waited for
After dissolving completely, the n-trimethyl chitosan chloride derivative solution obtained by step (1) is added by a certain percentage, low temperature stirs and evenly mixs, old
Change, the multi-functional temperature sensitive gel composite dressing of the wound healing is made；The dressing include n-trimethyl chitosan chloride derivative and
The mass ratio of terminal aldehyde group temperature sensitive polymer, two kinds of components is 1:15~1:25.
2. the wound healing according to claim 1 preparation method of multi-functional temperature sensitive gel composite dressing, feature
It is, the molecular weight of the chitosan of step (1) the n-trimethyl chitosan chloride derivative is 10~1,000,000, and deacetylation is
90% or more, quaternized degree of substitution is 10%~45%.
3. the wound healing according to claim 1 preparation method of multi-functional temperature sensitive gel composite dressing, feature
It is, step (1) and step (2) described buffer solution are that disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution, acetic acid-sodium acetate are slow
Fliud flushing, citric acid-sodium citrate buffer solution or citric acid-sodium hydroxide-hydrochloride buffer；Step (1) described heating stirring
Temperature is 25~60 DEG C, and the time is 12~36 hours.
4. the wound healing according to claim 1 preparation method of multi-functional temperature sensitive gel composite dressing, feature
It is, the terminal aldehyde group temperature sensitive polymer described in step (2) is prepared by following steps：Add in Pluronic F127
Enter the acetic anhydride of 10 times of moles, stirs lower instillation dmso solution, react 6~12h at 20~50 DEG C；After from
The heart, supernatant are precipitated with anhydrous ether, are filtered, are dried to obtain terminal aldehyde group temperature sensitive polymer.
5. the wound healing according to claim 1 preparation method of multi-functional temperature sensitive gel composite dressing, feature
It is, the low temperature described in step (2) is set as 4~15 DEG C.
6. the wound healing according to claim 1 preparation method of multi-functional temperature sensitive gel composite dressing, feature
It is, the time of step (2) described ageing is 12~24 hours.
7. the wound healing according to claim 1 preparation method of multi-functional temperature sensitive gel composite dressing, feature
It is, the rotating speed of the stirring described in step (1) and step (2) is 100~1000 revs/min.
Priority Applications (1)
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| US20200215284A9 (en) * | 2016-12-22 | 2020-07-09 | E-PROSPERITY & DEVELOPMENT CO., Ltd. | Airway device |
| CN108904875B (en) * | 2018-07-02 | 2023-09-22 | 西安交通大学 | Antibacterial self-healing hydrogel auxiliary material for promoting chronic wound healing and preparation method and application thereof |
| CN109106977B (en) * | 2018-08-27 | 2021-06-11 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | Self-healing injectable hydrogel dressing for diabetic wound repair and preparation method and application thereof |
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| CN110522718A (en) * | 2019-09-11 | 2019-12-03 | 大连医科大学 | A kind of injectable thermosensitive hydrogel and preparation method thereof |
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| CN114432493B (en) * | 2021-12-23 | 2023-06-27 | 南方医科大学顺德医院(佛山市顺德区第一人民医院) | Injectable biodegradable temperature-sensitive hydrogel and application thereof |
| CN114767922B (en) * | 2022-03-15 | 2023-09-12 | 青岛大学 | Hyaluronic acid hydrogel carrying probiotics and preparation method and application thereof |
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